Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

VX15/2503 and Immunotherapy in Resectable Pancreatic and Colorectal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03373188
Recruitment Status : Recruiting
First Posted : December 14, 2017
Last Update Posted : August 19, 2020
Sponsor:
Collaborator:
Vaccinex Inc.
Information provided by (Responsible Party):
Christina Wu, Emory University

Tracking Information
First Submitted Date  ICMJE December 11, 2017
First Posted Date  ICMJE December 14, 2017
Last Update Posted Date August 19, 2020
Actual Study Start Date  ICMJE December 15, 2017
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 21, 2018)
Evaluate treatment effects of the study drugs on tumor cluster of differentiation 8+ (CD8+) T cell infiltration between the treatment groups. [ Time Frame: Up to 4 years from date of last treatment dose ]
CD8+ T cells in tumor samples will be identified by immunohistochemistry and immunofluorescence staining, and we will quantitate the percentage and staining of the cells in the pancreatic and liver tissue with Integrated Cellular Imaging.
Original Primary Outcome Measures  ICMJE
 (submitted: December 11, 2017)
Immune profile in the tumor microenvironment and in peripheral blood [ Time Frame: Up to 4 years from the date of last treatment dose ]
Data for continuous parameters will be presented using descriptive statistics including sample size, mean, and median; standard deviation; and minimum and maximum.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 11, 2017)
Incidence of adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events scale version 4.0 [ Time Frame: Up to 4 years from the date of last treatment dose ]
Summary statistics will be presented for all safety analyses. Toxicities will be presented as worst toxicity per patient and will be reported as percent toxicity. Adverse events will be classified using MedDRA System Organ Classes and Preferred Terms.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE VX15/2503 and Immunotherapy in Resectable Pancreatic and Colorectal Cancer
Official Title  ICMJE Phase I Integrated Biomarker Trial of VX15/2503 in Combination With Ipilimumab or Nivolumab in Patients With Pancreatic and Colorectal Cancer
Brief Summary This randomized phase I trial studies how well anti-semaphorin 4D (anti-SEMA4D) monoclonal antibody VX15/2503 with or without ipilimumab or nivolumab work in treating patients with stage I-III pancreatic cancer that can be removed by surgery or stage IV colorectal cancer that has spread to the liver and can be removed by surgery. Monoclonal antibodies, such as anti-SEMA4D monoclonal antibody VX15/2503, ipilimumab, and nivolumab, may interfere with the ability of tumor cells to grow and spread.
Detailed Description

PRIMARY OBJECTIVE:

To evaluate the effect of the anti-SEMA4D monoclonal antibody VX15/2503 (VX15/2503) alone and VX15/2503 in combination with immune checkpoint inhibitors, ipilimumab or nivolumab, on the immune profile in the tumor microenvironment and in peripheral blood.

SECONDARY OBJECTIVE:

To extend the previously reported safety profile of single agent VX15/2503 to the combination of VX15/2503 and immune checkpoint inhibitors, ipilimumab or nivolumab, in patients with pancreatic and colorectal cancer.

OUTLINE:

Patients are randomized to 1 of 4 arms.

ARM I: Patients undergo surgery.

ARM II: Patients receive anti-SEMA4D monoclonal antibody VX15/2503 intravenously (IV) over 60 minutes on day 1. Patients then proceed to surgery 22-36 days after drug administration.

ARM III: Patients receive anti-SEMA4D monoclonal antibody VX15/2503 IV over 60 minutes and ipilimumab IV over 90 minutes on day 1. Patients then proceed to surgery 22-36 days after drug administration.

ARM IV: Patients receive anti-SEMA4D monoclonal antibody VX15/2503 IV over 60 minutes and nivolumab IV over 60 minutes on day 1. Patients then proceed to surgery 22-36 days after drug administration.

After completion of study treatment, patients are followed up at 90 days and then every 12 weeks thereafter.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Colon Carcinoma Metastatic in the Liver
  • Colorectal Adenocarcinoma
  • Pancreatic Adenocarcinoma
  • Resectable Pancreatic Carcinoma
  • Stage I Pancreatic Cancer
  • Stage IA Pancreatic Cancer
  • Stage IB Pancreatic Cancer
  • Stage II Pancreatic Cancer
  • Stage IIA Pancreatic Cancer
  • Stage IIB Pancreatic Cancer
  • Stage III Pancreatic Cancer
  • Stage IV Colorectal Cancer
  • Stage IVA Colorectal Cancer
  • Stage IVB Colorectal Cancer
Intervention  ICMJE
  • Biological: Anti-SEMA4D Monoclonal Antibody VX15/2503
    Given IV
    Other Names:
    • moAb VX15/2503
    • VX15/2503
  • Biological: Ipilimumab
    Given IV
    Other Names:
    • BMS-734016
    • MDX-010
    • MDX-CTLA4
    • Yervoy
  • Biological: Nivolumab
    Given IV
    Other Names:
    • BMS-936558
    • MDX-1106
    • NIVO
    • ONO-4538
    • Opdivo
  • Procedure: Surgery
    Undergo therapeutic conventional surgery
Study Arms  ICMJE
  • Active Comparator: Arm I (surgery)
    Patients undergo surgery.
    Intervention: Procedure: Surgery
  • Experimental: Arm II (VX15/2503, surgery)
    Patients receive anti-SEMA4D monoclonal antibody VX15/2503 IV over 60 minutes on day 1. Beginning 22-36 days after administration, patients undergo surgery.
    Interventions:
    • Biological: Anti-SEMA4D Monoclonal Antibody VX15/2503
    • Procedure: Surgery
  • Experimental: Arm III (VX15/2503, ipilimumab, surgery)
    Patients receive anti-SEMA4D monoclonal antibody VX15/2503 IV over 60 minutes and ipilimumab IV over 90 minutes on day 1. Beginning 22-36 days after administration, patients undergo surgery.
    Interventions:
    • Biological: Anti-SEMA4D Monoclonal Antibody VX15/2503
    • Biological: Ipilimumab
    • Procedure: Surgery
  • Experimental: Arm IV (VX15/2503, nivolumab, surgery)
    Patients receive anti-SEMA4D monoclonal antibody VX15/2503 IV over 60 minutes and nivolumab IV over 60 minutes on day 1. Beginning 22-36 days after administration, patients undergo surgery.
    Interventions:
    • Biological: Anti-SEMA4D Monoclonal Antibody VX15/2503
    • Biological: Nivolumab
    • Procedure: Surgery
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 11, 2017)
32
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2022
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • For patients with pancreatic cancer:

    • Stage I-III cytologically or histologically-proven pancreatic adenocarcinoma
    • Cancer confirmed to be surgically resectable, with surgery evaluation with planned resection
    • Patients may have prior neoadjuvant chemotherapy, but no neoadjuvant chemoradiation
    • No cancer chemotherapy treatment 2 weeks prior to day 2 of treatment
  • For patients with metastatic colorectal cancer:

    • Stage IV histologically-proven colorectal adenocarcinoma
    • Liver metastasis confirmed to be surgically resectable, with surgery evaluation and planned resection; may have minimal extrahepatic disease that is determined to be resectable
    • Tumor must be confirmed to be microsatellite stable (MSS); if not already reported at a Clinical Laboratory Improvement Act (CLIA)-certified laboratory, we will be able to perform this at Emory University
    • No prior immunotherapy
    • No cancer chemotherapy treatment 2 weeks prior to day 1 of treatment
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Absolute neutrophil count ≥ 1,500 cells/µL
  • Platelets ≥ 100,000/µL
  • Hemoglobin ≥ 9.0 g/dL (may receive packed red blood cell [prbc] transfusion)
  • Total bilirubin ≤ 1.5 x the upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
  • Albumin ≥ 3.0 g/dL
  • Serum creatinine ≤ 1.5 x ULN
  • Calculated creatinine clearance of ≥ 50 mL/min
  • International normalized ratio (INR) ≤ 1.5; anticoagulation is allowed only with low molecular weight heparin (LMWH); patient receiving LMW heparin on stable therapeutic dose for more than 2 weeks or with factor Xa level < 1.1 U/mL are allowed on the trial
  • Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
  • Ability to understand and willingness to sign a written informed consent document
  • Female subjects of childbearing potential must agree to use adequate contraception (e.g., hormonal or barrier method of birth control; abstinence) for the duration of study treatment and 3 months after completion
  • Male subjects must agree to use adequate contraception (e.g., condoms; abstinence) for the duration of study treatment and 3 months after completion
  • Female subjects of childbearing age must have a negative serum pregnancy test at study entry

Exclusion Criteria:

  • Poor venous access for study drug administration
  • Determined not to be a surgical candidate due to medical co-morbidities
  • Treatment with chronic immunosuppressants (e.g., cyclosporine following transplantation)
  • Prior organ allograft or allogeneic bone marrow transplantation
  • Subjects with any active autoimmune disease or history of known or suspected autoimmune disease except for subjects with vitiligo, resolved childhood asthma/atopy, type I diabetes mellitus, residual hypothyroidism, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
  • Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration; inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
  • Women who are pregnant or lactating
  • Uncontrolled intercurrent illness including, but not limited to, human immunodeficiency virus (HIV)-positive subjects receiving combination antiretroviral therapy, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association [NYHA] class III or IV), unstable angina pectoris, ventricular arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Other medications, or severe acute/chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study
  • Clinical evidence of bleeding diathesis or coagulopathy
  • Patients with prior malignancies, including pelvic cancer, are eligible if they have been disease free for > 5 years; patients with prior in situ carcinomas are eligible provided there was complete removal
  • Active bacterial or fungal infections requiring systemic treatment within 7 days of treatment
  • Use of other investigational drugs (drugs not marked for any indication) within 28 days or at least 5 half-lives (whichever is longer) before study drug administration
  • History of severe hypersensitivity reactions to other monoclonal antibodies
  • Non-oncology vaccines within 28 days prior to or after any dose of ipilimumab
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Christina Wu, MD 404-778-2670 christina.wu@emoryhealthcare.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03373188
Other Study ID Numbers  ICMJE IRB00098707
NCI-2017-01618 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
Winship4142-17 ( Other Identifier: Emory University Hospital/Winship Cancer Institute )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Christina Wu, Emory University
Study Sponsor  ICMJE Emory University
Collaborators  ICMJE Vaccinex Inc.
Investigators  ICMJE
Principal Investigator: Christina Wu, MD Emory University
PRS Account Emory University
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP